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Here, we identified the novel lncRNA GRASLND (originally named RNF144A-AS1) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. GRASLND, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SOX9, but not TGF-\u03b23. We showed that the silencing of GRASLND resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while GRASLND overexpression \u2013 either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 \u2013 significantly enhanced cartilage matrix production. GRASLND acts to inhibit IFN-\u03b3 by binding to EIF2AK2, and we further demonstrated that GRASLND exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of GRASLND in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.<\/jats:p>","DOI":"10.7554\/elife.49558","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T09:00:18Z","timestamp":1584954018000},"source":"Crossref","is-referenced-by-count":36,"title":["Long non-coding RNA GRASLND enhances chondrogenesis via suppression of the interferon type II signaling pathway"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-1645","authenticated-orcid":true,"given":"Nguyen PT","family":"Huynh","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Department of Cell Biology, Duke University, Durham, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine C","family":"Gloss","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremiah","family":"Lorentz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruhang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M","family":"Brunger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"McAlinden","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0330","authenticated-orcid":true,"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Washington University, St Louis, United States"},{"name":"Shriners Hospitals for Children, St. Louis, United States"},{"name":"Center of Regenerative Medicine, Washington University, St Louis, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2020,3,23]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.molmed.2017.08.002","article-title":"Genome engineering for personalized arthritis therapeutics","volume":"23","author":"Adkar","year":"2017","journal-title":"Trends in Molecular Medicine"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nature Methods"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1172\/JCI112041","article-title":"Influences of gamma interferon on synovial fibroblast-like cells. 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